Synthesis of Clinical-Grade [18F]-Fluoroestradiol as a Surrogate PET Biomarker for the Evaluation of Estrogen Receptor-Targeting Therapeutic Drug

Abstract

16α-[18F]-fluoroestradiol ([18F]FES), a steroid-based positron emission tomography (PET) tracer, has emerged as a dependable tracer for the evaluation and management of estrogen receptor-positive (ER+) breast cancer patients. We have developed a fully automatic, one-pot procedure for the synthesis of [18F]FES using the Eckert & Ziegler (E & Z) radiomodular system. After [18F]fluorination, the intermediate was hydrolyzed with 2.0 M HCl twice and neutralized with sodium bicarbonate. After high-performance liquid chromatography (HPLC) purification, the decay-corrected radiochemical yield and purity of [18F]FES were 40 ± 5.0% (n=12) and >97%, respectively. The product was stable up to 10 h. Total synthesis time including HPLC purification was 80 min. This new, fully automated rapid synthetic procedure provided high and reproducible yields of [18F]FES. Quality control (QC) tests showed that the [18F]FES produced by this method met all specifications for human injection.